ASH Clinical News ACN_4.12_Full book Web | Page 11

Bronchitis 55 (14) 5 (1) 40 (10) 2 (1)
Viral upper respiratory tract infection 55 (14) 0 (0) 44 (11) 0 (0)
Pneumonia a 54 (14) 35 (9) 43 (11) 27 (7)
Hypokalemia 78 (20) 22 (6) 35 (9) 12 (3)
Hypocalcemia 55 (14) 10 (3) 39 (10) 5 (1)
Hyperglycemia 43 (11) 18 (5) 33 (9) 15 (4)
Metabolism and Nutrition Disorders
Musculoskeletal and Connective Tissue Disorders
Muscle spasms 92 (24) 3 (1) 75 (19) 3 (1)
Back pain 41 (11) 4 (1) 54 (14) 6 (2)
43 (11) 7 (2) 39 (10) 4 (1)
64 (16) 6 (2) 51 (13) 8 (2)
Nervous System Disorders
Peripheral neuropathies b
Psychiatric Disorders
Insomnia
Respiratory, Thoracic, and Mediastinal Disorders
Cough c 93 (24) 2 (1) 54 (14) 0 (0)
Dyspnea d 71 (18) 8 (2) 61 (16) 6 (2)
45 (12) 5 (1) 54 (14) 5 (1)
Embolic and thrombotic events e 49 (13) 16 (4) 23 (6) 9 (2)
Hypertension 41 (11) 12 (3) 15 (4) 4 (1)
Skin and Subcutaneous Tissue Disorders
Rash
Vascular Disorders
f
KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone.
a
Pneumonia includes pneumonia and bronchopneumonia.
b
Peripheral neuropathies includes peripheral neuropathy, peripheral sensory neuropathy, and peripheral
motor neuropathy.
c
Cough includes cough and productive cough.
d
Dyspnea includes dyspnea and dyspnea exertional.
e
Embolic and thrombotic events, venous include deep vein thrombosis, pulmonary embolism,
thrombophlebitis superficial, thrombophlebitis, venous thrombosis limb, post thrombotic syndrome,
venous thrombosis.
f
Hypertension includes hypertension, hypertensive crisis.
There were 274 (70%) patients in the KRd arm who received treatment beyond Cycle 12. There were no new
clinically relevant adverse reactions that emerged in the later treatment cycles.
Grade 3 and higher adverse reactions that occurred during Cycles 1–12 with a substantial difference (≥ 2%)
between the two arms were neutropenia, thrombocytopenia, hypokalemia, and hypophosphatemia.
Safety Experience with Kyprolis in Combination with Dexamethasone in Patients with Multiple Myeloma
The safety of Kyprolis in combination with dexamethasone was evaluated in an open-label, randomized trial
of patients with relapsed multiple myeloma. Patients received treatment for a median duration of 48 weeks
in the Kyprolis/dexamethasone (Kd) arm and 27 weeks in the bortezomib/dexamethasone (Vd) arm.
Deaths due to adverse reactions within 30 days of last study treatment occurred in 32/463 (7%) patients
in the Kd arm and 21/456 (5%) patients in the Vd arm. The causes of death occurring in patients (%) in
the two arms (Kd vs. Vd) included cardiac 4 (1%) versus 5 (1%), infections 8 (2%) versus 8 (2%), disease
progression 7 (2%) versus 4 (1%), pulmonary 3 (1%) versus 2 (< 1%), renal 1 (< 1%) versus 0 (0%), and
other adverse events 9 (2%) versus 2 (< 1%). Serious adverse reactions were reported in 59% of the
patients in the Kd arm and 40% of the patients in the Vd arm. In both treatment arms, pneumonia was
the most commonly reported serious adverse reaction (8% vs. 9%). Discontinuation due to any adverse
reaction occurred in 29% in the Kd arm versus 26% in the Vd arm. The most common reaction leading
to discontinuation was cardiac failure in the Kd arm (n = 8, 2%) and peripheral neuropathy in the Vd arm
(n = 22, 5%).
Most Common Adverse Reactions (≥ 10% in the Kd Arm) Occurring in Months 1–6 (20/56 mg/m 2
Regimen in Combination with Dexamethasone)
Kd
(N = 463), n (%)
Adverse Reaction by Body System
Vd
(N = 456), n (%)
Any Grade ≥ Grade 3 Any Grade
≥ Grade 3
Anemia 161 (35) 57 (12) 112 (25) 43 (9)
Thrombocytopenia a 125 (27) 45 (10) 112 (25) 64 (14)
Diarrhea 117 (25) 14 (3) 149 (33) 27 (6)
Nausea 70 (15) 4 (1) 68 (15) 3 (1)
Constipation 60 (13) 1 (0) 113 (25) 6 (1)
Vomiting 45 (10) 5 (1) 33 (7) 3 (1)
Blood and Lymphatic System Disorders
Gastrointestinal Disorders
General Disorders and Administration Site Conditions
Fatigue 116 (25) 14 (3) 126 (28) 25 (6)
Pyrexia 102 (22) 9 (2) 52 (11) 3 (1)
Asthenia 73 (16) 9 (2) 65 (14) 13 (3)
Peripheral edema 62 (13) 3 (1) 62 (14) 3 (1)
Upper respiratory tract infection 67 (15) 4 (1) 55 (12) 3 (1)
Bronchitis 54 (12) 5 (1) 25 (6) 2 (0)
Infections and Infestations
Musculoskeletal and Connective Tissue Disorders
Muscle spasms 70 (15) 1 (0) 23 (5) 3 (1)
Back pain 64 (14) 8 (2) 61 (13) 10 (2)
Headache 67 (15) 4 (1) 39 (9) 2 (0)
Peripheral neuropathies b 56 (12) 7 (2) 170 (37) 23 (5)
Nervous System Disorders
Psychiatric Disorders
Insomnia
105 (23)
5 (1) 116 (25) 10 (2)
Respiratory, Thoracic, and Mediastinal Disorders
Dyspnea c 123 (27) 23 (5) 66 (15) 8 (2)
Cough 97 (21) 0 (0) 61 (13) 2 (0)
83 (18) 30 (7) 33 (7) 12 (3)
d
Vascular Disorders
Hypertension e
Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone.
a
Thrombocytopenia includes platelet count decreased and thrombocytopenia.
b
Peripheral neuropathies include peripheral neuropathy, peripheral sensory neuropathy, and peripheral
motor neuropathy.
c
Dyspnea includes dyspnea and dyspnea exertional.
d
Cough includes cough and productive cough.
e
Hypertension includes hypertension, hypertensive crisis, and hypertensive emergency.
The event rate of ≥ Grade 2 peripheral neuropathy in the Kd arm was 7% (95% CI: 5, 9) versus 35%
(95% CI: 31, 39) in the Vd arm.
6.2 Postmarketing Experience
The following additional adverse reactions were reported in the postmarketing experience with Kyprolis.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal relationship to drug exposure: hemolytic
uremic syndrome (HUS), gastrointestinal perforation, pericarditis.
8. USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Kyprolis can cause fetal harm based on findings from animal studies and the drug’s mechanism of action.
There are no adequate and well-controlled studies in pregnant wom